The present invention is generally in the area of immunoregulation, and is particularly the selective hormone-mediated modulation of lymphocyte formation in bone marrow.
The formation of lymphocytes and other blood cells is a carefully regulated process that is essential for maintenance of a normal immune system. Lymphocytes responsible for antibody formation, B lymphocytes, are made in bone marrow. Another major category of lymphocytes, T lymphocytes, is made in the thymus. Together these lymphocytes are responsible for both the humoral (antibody) mediated immune response and the cell mediated immune response.
Studies of molecular regulators of B lymphopoiesis have focused on aspects that might be organ, i.e., bone marrow, specific. However, to date, no molecules have been found which are unique to that tissue.
There is a gradual atrophy of the thymus with age, but the mechanism through which this occurs is not known. It has also long been known that the thymus atrophies during pregnancy and regenerates after delivery. There is reason to believe that this phenomenon is regulated by hormones, because estrogen injections have been observed to cause similar thymus atrophy. However, the immune system is thought to function normally during pregnancy, that is, the host defense against pathogens is intact.
A better understanding of the influence of hormones on the humoral immune system is needed. This information may be relevant to maternal--fetal relationships during pregnancy and abnormalities involving them, as well as to the pathophysiologic mechanisms of autoimmune diseases such as systemic lupus erythematosus (SLE), which are commonly diagnosed or worsen during pregnancy. The same is true of diseases such as cyclic neutropenia, which may have a basis in hormonal dysfunction. An increased awareness of the effect of hormone administration may also help prevent iatrogenic disease or the side effects of hormones replacement therapy, such as in the treatment of osteoporosis. It may also be possible to utilize this basic information to manipulate immunologic tolerance and achieve immunosuppression, or alternatively, with hormone antagonists, to augment the humoral immune system. Moreover, methods for propagating lympho-hemopoietic progenitor cells and stem cells in culture might be improved by manipulation of hormone concentrations in cell culture medium.
It is therefore an object of the present invention to provide a method for immunomodulation through manipulation of specific classes of immune cells, especially B lymphocytes, by administration of compounds having an effect on the number of B lymphocyte precursors.
It is a further object of the present invention to provide methods and means for manipulation of B lymphocytes involved in autoimmune disorders, osteoporosis, and cyclic neutropenia.
It is another object of the present invention to provide methods and means to improve cell culture of bone marrow and stromal cells.